Conventionally, MRI has been used to produce images by exciting the nuclei of hydrogen molecules (present in water protons) in the human body. However, it has recently been discovered that polarized noble gases can produce improved images of certain areas and regions of the body, which have heretofore produced less than satisfactory images in this modality. Polarized .sup.3 He and Xenon-129 (".sup.129 Xe") have been found to be particularly suited for this purpose. Unfortunately, as will be discussed further below, the polarized state of the gases are sensitive to handling and environmental conditions and, undesirably, can decay from the polarized state relatively quickly.
"Polarization" or hyperpolarization of certain noble gas nuclei (such as .sup.129 Xe or .sup.3 He) over the natural or equilibrium levels, i.e., the Boltzmann polarization, is desirable because it enhances and increases MRI signal intensity, allowing physicians to obtain better images of the substance in the body. See U.S. Pat. No. 5,545,396 to Albert et al., the disclosure of which is hereby incorporated herein by reference as if recited in full herein.
For medical applications, after the hyperpolarized gas is produced, it is processed to form a non-toxic or sterile composition prior to introduction into a patient. Unfortunately, during and after collection, the hyperpolarized gas can deteriorate or decay (lose its hyperpolarized state) relatively quickly and therefore must be handled, collected, transported, and stored carefully. The "T.sub.1 " decay constant associated with the hyperpolarized gas' longitudinal relaxation time is often used to describe the length of time it takes a gas sample to depolarize in a given container. The handling of the hyperpolarized gas is critical, because of the sensitivity of the hyperpolarized state to environmental and handling factors and the potential for undesirable decay of the gas from its hyperpolarized state prior to the planned end use, i.e., delivery to a patient. Processing, transporting, and storing the hyperpolarized gases--as well as delivery of the gas to the patient or end user--can expose the hyperpolarized gases to various relaxation mechanisms such as magnetic gradients, ambient and contact impurities, and the like.
In the past, various hyperpolarized delivery modes such as injection and inhalation have been proposed to introduce the hyperpolarized gas to a patient. Inhalation of the hyperpolarized gas is typically preferred for lung or respiratory type images. To target other regions, other delivery paths and techniques can be employed. However, because helium is much less soluble than xenon in conventional carrier fluids such as lipids or blood, .sup.3 He has been used almost exclusively to image the lungs rather than other target regions.
Recent developments have proposed overcoming the low solubility problem of helium by using a micro-bubble suspension. See Chawla et al., In vivo magnetic resonance vascular imaging using laser-polarized .sup.3 He microbubbles, 95 Proc. Natl. Acad. Sci. USA, pp. 10832-10835 (September 1998). Chawla et al. suggests using radiographic contrast agents as the injection fluid to deliver microbubbles of hyperpolarized .sup.3 He gas in an injectable formulation. This formulation can then be injected into a patient in order to image the vascular system of a patient.
Generally stated, one way currently used to load or produce the microbubble mixture is via "passive" permeability. That is, the hyperpolarized .sup.3 He typically enters the walls of the micro-bubbles based on the helium permeability of the bubble itself. Thus, this gas loading method can take an undesirable amount of time, which can allow the hyperpolarized gas to decay unduly. Further, contact with the fluid or even the microbubble can result in contact-induced depolarization which can dominate the relaxation mechanisms of the hyperpolarized .sup.3 He and cause an undesirable reduction in the hyperpolarized life of the gas.
As such, there remains a need to improve micro-bubble .sup.3 He formulations and loading methods to minimize the decay of the polarized gas and improve the T.sub.1 of the micro-bubble formulation.
In addition, there is also a need to increase the ease of solubilizing hyperpolarized gaseous xenon, which, in the past, has been problematic.